Food restriction therapy has been used clinically for over a hundred years to treat obesity and type 2 diabetes. Animal studies have confirmed that food restriction has a regulatory and restorative effect on various systems such as cardiovascular and brain degenerative pathologies and autoimmune diseases in the context of slowing down aging and extending life span. During the development of clinical applications, food restriction therapy has made leaps and bounds in terms of form, indications, and efficacy in preventing and treating diseases, and has gradually accumulated some evidence of evidence-based medicine. In this paper, we review the research progress of food restriction therapy in the prevention and treatment of metabolic diseases in 2014.
1. Diversification of food restriction modalities
1.1 Intermittent food restriction is popular, and alternate-day restriction stands out
Traditional daily food restriction (20-50% of total calories) is still the main dietary intervention recommended by current guidelines for patients with obesity and type 2 diabetes. However, in recent years, intermittent restriction is gaining acceptance among scholars and patients because of its ease of implementation and comparable effectiveness. Intermittent restriction refers to restricting food for 1-3 days of the week and eating freely for the rest of the week, as exemplified by the currently prevalent 5+2 restriction protocol. Alternating day restriction is a derivative of intermittent restriction and can be considered a subcategory of intermittent restriction in which the restrictor eats normally one day and restricts 75% of the food on one day, alternately.
Varady et al. have conducted numerous studies on alternate day restriction in animals and humans. In a 2014 review, they analyzed the effect of intermittent/every-other-day restriction compared to daily restriction on the prevention of diabetes. The results found [1] that weight loss was slightly more significant in the daily restriction group compared to intermittent/every-other-day restriction, with 3-8% weight loss in the former group for 3-24 weeks of intervention and 4-14% weight loss in the latter group for 6-24 weeks of intervention; the trend was similar for visceral fat content. Fasting insulin and insulin resistance index decreased significantly in both groups to a comparable extent. However, when comparing changes in blood glucose levels in the prediabetic population, the results differed, with a 3-6% decrease in blood glucose in the intermittent/every-other-day restriction group and no significant change in blood glucose in the daily restriction group, which may be related to the duration of the latter intervention and the degree of caloric restriction. varady suggests that intermittent/every-other-day restriction would be an ideal alternative to long-term daily restriction for weight loss in overweight and obese people, and prevention of the development of type 2 diabetes [1]. However, long-term follow-up results from intermittent/every-other-day restriction and data from larger samples are necessary for clinicians to develop scientifically sound individualized restriction programs.
1.2 Eating restriction has shown superior results
In 2014, Panda and colleagues reported [2,3] that time-restricted feeding (continuous food supply for 9-15 hours of the day and no food for the rest of the day) prevented and reversed high-fat feeding-induced obesity and type 2 diabetes in mice, with effects The effect was proportional to the duration of time restriction, which may be related to the regulation of intestinal flora by time restricted feeding. The proposed feeding pattern challenges the clinical pattern of eating fewer and more frequent meals in diabetic patients. Whether extended fasting times throughout the day are beneficial for patients with metabolic disorders is unknown and needs to be supported by further clinical studies.
1.3 The advantages and disadvantages of component restriction are controversial
Component restriction, as the name implies, limits the amount of a specific component (e.g., carbohydrate or fat) in the diet. Component restriction is used in the treatment of some specific diseases.
The ketogenic (carbohydrate <50 g/d) diet, first used in 1820 for epilepsy and in 1960 for obese patients, has recently been found to have therapeutic effects in oncology, type 2 diabetes, polycystic ovary syndrome, cardiovascular, and neurological disorders, reducing the adverse effects associated with long-term medication [4].In 2014, Paoli et al [5] reviewed the use of the ketogenic diet in In 2014, Paoli et al [5] reviewed the application of ketogenic diet in the treatment of obesity and concluded that ketogenic diet is a favorable weapon in the treatment of obesity and clinicians should properly understand and reasonably use it. The ketogenic diet exerts its weight reduction effect through the following ways. First, the proportion of protein in the ketogenic diet increases, which increases the feeling of satiety; the ketone body produced by restricting carbohydrates itself has an appetite suppressing effect, and the patient feels less hungry and eats less. Secondly, ketogenic diet promotes fat oxidation metabolism and reduces adipogenesis. Furthermore, when carbohydrates are insufficient and the body uses protein for energy, the amount of calories consumed is greatly increased. Generally the ketogenic diet can be as short as 2-3 weeks (to induce physiological ketosis) and as long as 6-12 months (for disease prevention purposes). Monitoring of renal function is required before and during the implementation of the ketogenic diet, with a slow transition to a normal diet after its completion.
Both low-fat restriction and low-carbohydrate restriction (restriction of fat or carbohydrates without restriction of total calories) have been reported to improve NAFLD. 2013, Li Chunrui et al [6] reviewed the relevant literature and found that in patients with NAFLD, low-calorie restriction, low-carbohydrate restriction, and low-fat restriction were all significantly effective, with patients having reduced body weight, increased insulin sensitivity and high-density lipoprotein cholesterol In 2014, Jonasson et al [7] reported that a low-carbohydrate diet (20% carbohydrate energy supply) was similar to a low-fat diet (55-60% carbohydrate energy supply) in terms of weight loss in patients with type 2 diabetes, but A low-carbohydrate diet also reduces the inflammatory response in type 2 diabetic patients, which is not seen in a low-fat diet, and therefore advocates controlled carbohydrate intake in type 2 diabetic patients.
However, it has also been argued that component restriction is not optimal. 2014 Meidenbauer et al [8] found in a study in mice that different nutrient composition (standard diet, ketogenic diet, fish oil supplemented diet) affected body weight, hormones, and metabolic indices in mice on ad libitum diet; however, the effects caused by different nutrient composition disappeared in the case of uniform diet restriction. They concluded that food restriction (caloric restriction) was the main and independent factor affecting metabolic indices and was not related to nutrient composition ratios; caloric restriction, not food component ratios, was essential for dietary interventions to prevent and treat metabolic diseases. In the same year, England et al [9] studied the relationship between dietary changes and glycated hemoglobin in patients with first-onset type 2 diabetes and found that changes in the proportion of nutrients in the diet did not correlate with improvements in metabolic indicators, but this idea needs to be supported by studies with larger samples, especially for populations with poor glycemic control.
In conclusion, there is no consistent conclusion as to which component of food restriction is superior for improving metabolic indicators. We believe that individualized diet restriction regimens can be developed clinically and flexibly to achieve the maximum benefit from the diet, depending on the specific condition of the patient.
1.4 The status of the Mediterranean diet remains
Strictly speaking, the Mediterranean diet does not belong to the category of dietary restriction; it is not a fixed single recipe, but a generalization of the dietary habits of the countries bordering the Mediterranean. In short, it is a diet rich in olive oil, vegetables, legumes, whole grains, fruits, and nuts, with moderate intake of poultry or fish, limited consumption of full-fat dairy products and red meat, and small to moderate amounts of red wine.
The Mediterranean diet is known to reduce the risk of cardiovascular disease, and recent studies focusing on the relationship between the Mediterranean diet and the prevention and treatment of type 2 diabetes have yielded promising results [10-11].In 2014, Georgoulis et al [12] and Ley et al [13] emphasized the preventive and therapeutic effects of the Mediterranean diet on diabetes. Adherence to the Mediterranean diet significantly reduced the development of type 2 diabetes in the general population, in people at high risk of cardiovascular disease, and in patients with cardiovascular disease. Patients with type 2 diabetes had better glycemic control in the Mediterranean diet group compared to the general diet group and the low-fat diet group. Interestingly, in 2014, Karamanos et al [14] reported that women who adhered to the Mediterranean diet had a reduced incidence of gestational diabetes.
Of interest is that the Mediterranean diet also has a significant preventive and therapeutic effect on complications and comorbidities of type 2 diabetes [12]. Compared with the low-fat diet group, the Mediterranean diet group had a reduced incidence of cardiovascular events and mortality, suggesting that this dietary pattern can be used for primary and secondary prevention of cardiovascular disease in diabetic patients; about 70% of type 2 diabetic patients have combined NAFLD, and the Mediterranean diet can improve liver function, increase insulin sensitivity, and reduce liver steatosis. In addition, the Mediterranean diet can also improve sexual function in type 2 diabetics.
2.Food restriction simulants are proliferating
The role of food restriction therapy in delaying aging and improving metabolism is clear, however, long-term adherence to food restriction is extremely challenging for patients. In recent years, some scholars have turned their attention to drugs that mimic caloric restriction for use in patients who are reluctant to control their diet or in healthy populations. Targeting the molecular mechanisms of the effects of food restriction, they explored drugs that induce metabolic, hormonal, and physiological effects similar to those of food restriction, activating a stress response similar to that of food restriction, and achieving a reduction in aging-related diseases, delaying aging, and extending lifespan without affecting eating [15].
Based on these principles, a wide variety of drugs with food restriction mimetic effects have been discovered [15]. Drugs acting from upstream mechanisms include: chitosan (chitosan), orlistat, and mannan oligosaccharides, which inhibit fat digestion and absorption; acarbose, which inhibits carbohydrate absorption; and glycolysis inhibitors 2-deoxyglucose, glucosamine, mancoheptulose, 3-bromopyruvate, and iodoacetates. Drugs that play a role downstream include: metformin, an inhibitor of the insulin action signaling pathway; resveratrol, nikethamide, oxaloacetate, etc., agonists of longevity proteins (Sirtuins); rapamycin, an inhibitor of the mTOR pathway. In addition, surgical weight reduction surgery, which reduces caloric intake by inhibiting the digestion and absorption of fats and carbohydrates and regulates the level of digestive tract hormones, thus achieving weight loss and improving metabolism, is also considered a typical program that mimics the effect of food restriction from upstream mechanisms.
Some of these drugs have been on the market for many years, most are in the development stage, and a few have been evaluated in clinical trials. Although there is not yet a drug named after the main effect of food restriction mimetics, their role in improving metabolism and maintaining the youthful vitality of the body bodes well for this field in the future.
3, the importance of the previous increase, nutritionists indispensable
Previous studies on food restriction were mostly in developed countries in Europe and the United States, and in recent years, Asian scholars began to pay attention to the importance of food restriction intervention. in 2014, Korean scholars restricted food for 12 weeks in 57 premenopausal obese women, with significant weight loss and improved insulin sensitivity, again emphasizing that for middle-aged obese women, weight loss is the first task to prevent diabetes [16]. In China, Professor Qin Jian of the Affiliated Hospital of Sun Yat-sen University introduced food restriction therapy from Germany in 2008, on the basis of which we carried out short-term very low calorie restriction, which was applied to patients with first-onset type 2 diabetes and achieved significant therapeutic effects and good safety [17].
The significance of dietary interventions to prevent and treat metabolic diseases such as type 2 diabetes cannot be overstated. Unfortunately, most patients do not consult a dietitian, and dietetic consultations are rare, and long-term outpatient follow-up is deficient, leading to misconceptions about diet restriction in many patients. 2014, Vetter et al [18] interpreted the American Diabetes Association (ADA) medical nutrition guidelines for patients with type 2 diabetes [19]. treatment guidelines [19], advocating the development of flexible individualized dietary regimens that emphasize total carbohydrate intake (rather than type) and reduce fat intake. In overweight or obese patients with type 2 diabetes, different forms of dietary restriction, such as low-carbohydrate restriction, low-fat restriction, low glycemic index restriction, and the Mediterranean diet, can be used to achieve a goal of 5-10% weight loss; a weight loss of 4.5 kg can lead to a reduction in glycated hemoglobin of approximately 0.5%. Emphasize that dietitians, or diabetes educators with knowledge of nutrition should participate and intervene in the health management of diabetic patients throughout the process.
4. Opportunities and challenges exist, and the evidence-based basis is still missing.
Despite the obvious advantages of food restriction therapy to prevent and treat metabolic diseases, there are still many limitations in its clinical application and consensus formation. Due to the influence of different dietary habits and cultural differences in different regions, it is extremely difficult to standardize variables such as the degree of calorie restriction, the number of days of food restriction, and food composition. Currently, food restriction therapy is mostly mentioned as a special adjunctive treatment in the medical nutrition treatment guidelines for diabetes. Only German experts developed consensus guidelines for fasting (a very low calorie restriction protocol) in 2013 to standardize the definition, indications, contraindications, operational procedures, safety and precautions of fasting therapy to promote its safe and effective implementation [20]. Therefore, it is evident that the evidence-based basis provided by high-quality randomized controlled studies will be the hot spot and focus of future research in the field of fasting.